Understanding the role of biofilm formation in the lifecycle of pathogenic Salmonella strains

点击翻译按钮获取中文摘要

The experiments in this proposal are designed to identify the nutritional signals that lead to Salmonella biofilm development, to explore the possibility that biofilms can form inside the host, and to better define the complex regulatory network that leads to their formation. The aggregation of cells into dense biofilms provides a distinct survival advantage under stressful conditions and we want to investigate how this contributes to the pathogenic success of Salmonella and related enteric pathogens. The Salmonella strains that cause gastroenteritis are responsible for thousands of food-borne infections each year in Canada and are thought to cycle back and forth between hosts and the environment. In contrast, Salmonella strains that cause systemic infections, such as typhoid fever, are thought to be transmitted directly from person to person, without a prolonged environmental phase. It is known that gastroenteritis strains are predominantly biofilm-positive and systemic strains are biofilm-negative; by comparing the phenotypes and genotypes of these groups of strains we will identify genomic signatures that are responsible for gain or loss of biofilm formation. Finally, as an extension of previous Discovery grant-funded research, we will work to identify roles of biofilm-related genes of unknown function in the persistence of Salmonella as well as genes that are activated as part of the adaptations required for cells to cause infections. The coordinated regulation of these genes is predicted to be part of the evolutionary adaptations that allow Salmonella to transition smoothly between host and non-host environments. My proposed research consists of targeted approaches examining specific genes, coupled with genome-wide analyses that involve next-generation sequencing. The intersection of the proposed avenues of research will lead to a greater understanding of the lifecycle of these important human pathogens and the potential roles of biofilm formation. My long-term research goal is to develop strategies to reduce the millions of Salmonella infections that are caused around the world each year.